In Vivo (Add solvents to the product individually and in order.)
Homogeneous suspension
CMC-NA
≥5mg/ml
Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO
40%PEG300
5%Tween80
50%ddH2O
Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.
4.300mg/ml
(9.93mM)
Taking the 1 mL working solution as an example, add 50 μL of 86 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution
5% DMSO
95% Corn oil
Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.
0.710mg/ml
(1.64mM)
Taking the 1 mL working solution as an example, add 50 μL of 14.2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)
Preparing Stock Solutions
Biological Activity
Description
ARS-853 is a selective, covalent KRAS(G12C) inhibitor that inhibits mutant KRAS-driven signalling by binding to the GDP-bound oncoprotein and preventing activation. This compound also induces apoptosis.
Targets
K-Ras(G12C) (in H358 cells)
2.5 μM
In vitro
ARS-853 treatment of KRASG12C cells led to a dose-dependent and nearly complete inhibition of CRAF-RBD (RBD)-mediated pulldown of KRAS from lysates, with an IC50 of approximately 1 μmol/L. Treatment of H358 cells by this compound resulted in a significant loss of KRAS–CRAF interactions. Consistent with an inactive state of KRASG12C once bound to this chemical, downstream signalling through both MAPK (including pMEK, pERK, and pRSK) and PI3K signalling (pAKT) pathways was inhibited by it in H358 and other KRASG12C cell lines. The inhibition of RAF-RBD pulldown and KRAS downstream signalling was sustained over a period of 72 hours, accompanied by G1 Cell Cycle arrest, loss of Cyclin D1 and Rb expression, and an increase in the Cell Cycle inhibitor p27 KIP1. In addition, hallmarks of Apoptosis related, including cleaved PARP and increases in sub-diploid DNA, were observed in H358 cells following treatment with this compound. No effects on RAF-RBD binding or downstream signalling were observed in A549 cells (KRASG12S), and the inhibitory effects of it in H358 cells could be rescued by ectopic expression of KRASG12V. KRASG12C is the most potent covalent target of this chemical across more than 2,700 cellular proteins and consistently find that it exerts no effects on cellular signalling or growth in non-KRASG12C cells at concentrations up to 10-fold higher than its KRASG12C potency. It reacts only with the inactive (GDP-bound), but the not the active (GTP-bound), state of KRAS. This compound reduced KRAS-GTP levels and ERK phosphorylation in human embryonic kidney 293 (HEK293) or H358 cells engineered to express KRASG12C but not in those expressing KRASG12C/A59G. It traps KRASG12C in a GDP-bound conformation by lowering its affinity for nucleotide exchange factors.
KRASG12C mutant cells (H358) were treated with ARS853 for 5 hours. The effect on the level of active, or GTP-bound, KRAS was determined by a RAS-binding domain pull-down (RBD:PD) assay and immunoblotting with a KRAS-specific antibody.
References
https://pubmed.ncbi.nlm.nih.gov/26739882/
https://pubmed.ncbi.nlm.nih.gov/26841430/
Sellecks ARS-853 Has Been Cited by 5 Publications
Real-time monitoring of the reaction of KRAS G12C mutant specific covalent inhibitor by in vitro and in-cell NMR spectroscopy
[ Sci Rep, 2023, 10.1038/s41598-023-46623-w]
RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.
SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.
NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.
